The goal of this research is to prepare synthetic and semisynthetic mitomycin analog that have improved therapeutic ratios in cancer chemotherapy. We plan to exploit differences between normal cells and certain cancer cells that are appropriate to the mitomycin molecules. These differences are the quinone reduction potential and the hydrophilicity of the molecules. New 1-substituted mitosene analogs which have good leaving groups, but which are not hydrolyzed by serum esterases will be prepared. Additional mitosane analogs based on our recent compounds that are almost as active as mitomycin C also will be emphasized. The total synthesis of an aziridinomitosene will be completed and new aziridinomitosene analogs will be prepared. Antitumor screening against P388 and L1210 leukemias in mice will be conducted by collaborative arrangement with Bristol Laboratories according to DRD protocols.